Shift from Polyploidizing to Nonpolyploidizing Growth in Carcinogen-treated Rat Liver

Liver growth patterns in normal and carcinogen-treated young Wistar Kyoto rats were analyzed in terms of absolute hepatocyte numbers and ploidy distributions, calculated from DNA measurements made by flow cytometry and microscope counts of binucleated cells. Polyploidizing growth was observed during normal liver development, dominated by progressive polyploidization and a decrease in the number of diploid cells. Nonpolyploidizing growth was seen during liver regeneration and after treatment with 2-acetylaminofluorene (AAF). This mode of growth was characterized by an increase in all mononucleated ploidy classes in the absence of net polyploidization (no increase in binucleated cells). Additional diploid proliferation was detected after initiation with diethylnitrosamine followed by promotion with AAF. This selectively expanding diploid hepatocyte population, which persisted after AAF withdrawal, could represent the AAF-promoted progeny of diethylnitrosamine-altered cells with constitutive nonpolyploidizing growth properties.